Citations

Background Pituitary carcinoma (PC) is an aggressive neuroendocrine tumor diagnosed when a pituitary adenoma (PA) becomes metastatic. PCs are typically resistant to therapy and develop multiple recurrences despite surgery, radiotherapy and chemotherapy. Recently, treatment with temozolomide (TMZ) has shown promising results, although the lack of prospective trials limits assessment of benefit. Methods We describe a single-center multidisciplinary experience in managing PC patients over a 22-year period and review previously published PC series. Results Seventeen patients were identified. Median age at PC diagnosis was 44 years (range 16–82 years), and the median time from PA to PC transformation was 5 years (range 1–29 years). Median follow-up time was 28 months. Most PCs were hormone-positive (n = 12): ACTH (n = 5), PRL (n = 4), LH/FSH (n = 2) and GH (n = 1). All patients underwent at least one resection and at least one course of radiation after PC diagnosis. Immunohistochemistry showed high Ki-67 labeling index (>3%) in 10/15 cases. Eight patients (47%) had only central nervous system (CNS) metastases; six (35%) had combined CNS and systemic metastases. The most commonly used chemotherapy was TMZ, and TMZ-based therapy was associated with the longest PFS in 12 (71%) cases, as well as the longest period from PC diagnosis to first progression (median 30 months). The 2, 3 and 5-year survival rate of the entire cohort was 71, 59 and 35%, respectively. All patients surviving >5 years had been treated with TMZ-based therapy. Conclusions PC management benefits from multidisciplinary care and multimodality therapy. TMZ-based regimens were associated with high survival rates and long disease control.

AbstractBackgroundGlioblastoma (GBM) represents an aggressive cancer type with a median survival of only 14 months. With fewer than 5% of patients surviving 5 years, comprehensive profiling of these rare patients could elucidate prognostic biomarkers that may confer better patient outcomes. We utilized multiple molecular approaches to characterize the largest patient cohort of isocitrate dehydrogenase (IDH)–wildtype GBM long-term survivors (LTS) to date.MethodsRetrospective analysis was performed on 49 archived formalin-fixed paraffin embedded tumor specimens from patients diagnosed with GBM at the Mayo Clinic between December 1995 and September 2013. These patient samples were subdivided into 2 groups based on survival (12 LTS, 37 short-term survivors [STS]) and subsequently examined by mutation sequencing, copy number analysis, methylation profiling, and gene expression.ResultsOf the 49 patients analyzed in this study, LTS were younger at diagnosis (P = 0.016), more likely to be female (P = 0.048), and MGMT promoter methylated (UniD, P = 0.01). IDH-wildtype STS and LTS demonstrated classic GBM mutations and copy number changes. Pathway analysis of differentially expressed genes showed LTS enrichment for sphingomyelin metabolism, which has been linked to decreased GBM growth, invasion, and angiogenesis. STS were enriched for DNA repair and cell cycle control networks.ConclusionsWhile our findings largely report remarkable similarity between these LTS and more typical STS, unique attributes were observed in regard to altered gene expression and pathway enrichment. These attributes may be valuable prognostic markers and are worth further examination. Importantly, this study also underscores the limitations of existing biomarkers and classification methods in predicting patient prognosis.

Abstract Background A better understanding of social determinants of health and psychosocial and economic sequelae of cancer for an ethnoculturally diverse population is needed. A Patient-Reported Outcomes Quality of Life (PROQOL) instrument has been developed to capture less commonly discussed patient concerns. We sought to adapt this instrument and pilot it in underserved, ethnic minority cancer patients at Maricopa Integrated Health System (MIHS) in Phoenix, AZ. Methods Two focus groups (FG) were conducted to understand patient perspectives of an adapted Spanish version of PROQOL. A revised version based on FG data was then piloted among patients on active cancer treatment. Patients also completed a Linear Analog Scale Assessment (from 1-10) for quality of life (QOL) and its domains. Results All participants in both FG (11/12 female) were Hispanic, with a median age of 53 years. Participants agreed that the domains covered in the PROQOL represented the most important psychosocial needs in their cancer continuum. No difficulty in understanding the individual domains or questions for delving deeper into each domain was noted. Median age of 34 pilot study participants (74% female, 79% Hispanic) was 48 years. 28/34 completed the Spanish version. The most common concerns were ‘Money’ (32%) and ‘Cancer Diagnosis, Treatment and Survivorship’ (32%). Median overall QOL was 8 (range 3-10). Conclusions PROQOL is feasible for systematic capture of patient concerns in underserved, ethnic minority cancer patients. A better understanding of these concerns can help design interventions to improve psychosocial outcomes for the vulnerable groups and decrease disparities in care delivery.

Background Endoscopic skull‐base surgery (ESBS) is employed in the management of diverse skull‐base pathologies. Paralleling the increased utilization of ESBS, the literature in this field has expanded rapidly. However, the rarity of these diseases, the inherent challenges of surgical studies, and the continued learning curve in ESBS have resulted in significant variability in the quality of the literature. To consolidate and critically appraise the available literature, experts in skull‐base surgery have produced the International Consensus Statement on Endoscopic Skull‐Base Surgery (ICAR:ESBS). Methods Using previously described methodology, topics spanning the breadth of ESBS were identified and assigned a literature review, evidence‐based review or evidence‐based review with recommendations format. Subsequently, each topic was written and then reviewed by skull‐base surgeons in both neurosurgery and otolaryngology. Following this iterative review process, the ICAR:ESBS document was synthesized and reviewed by all authors for consensus. Results The ICAR:ESBS document addresses the role of ESBS in primary cerebrospinal fluid (CSF) rhinorrhea, intradural tumors, benign skull‐base and orbital pathology, sinonasal malignancies, and clival lesions. Additionally, specific challenges in ESBS including endoscopic reconstruction and complication management were evaluated. Conclusion A critical review of the literature in ESBS demonstrates at least the equivalency of ESBS with alternative approaches in pathologies such as CSF rhinorrhea and pituitary adenoma as well as improved reconstructive techniques in reducing CSF leaks. Evidence‐based recommendations are limited in other pathologies and these significant knowledge gaps call upon the skull‐base community to embrace these opportunities and collaboratively address these shortcomings.

Omega-3 polyunsaturated fatty acids ( n-3 PUFAs) exert numerous beneficial biological effects and attenuate diet-induced insulin resistance in rodent models. In the present study, the independent, tissue-specific effects of two nutritionally relevant n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were characterized in the context of a high-fat diet (HFD). EPA and DHA supplementation (3.2% of total fat) in 6-mo-old male C57BL/6 mice fed an HFD (60% fat) partially mitigated reductions in insulin sensitivity. At 5 wk, the area above the curve below baseline glucose following an intraperitoneal insulin tolerance test was 54.5% lower in HFD than control, whereas HFD + EPA and HFD + DHA showed 27.6% and 17.1% reductions, respectively. At 10 wk, HFD increased mitochondrial oxidative capacity supported by lipid and carbohydrate-based substrates in both liver and skeletal muscle ( P < 0.05), with little effect of EPA or DHA supplementation. Whole genome transcriptomic analyses revealed HFD-induced transcriptional changes indicative of inflammation and fibrosis in both liver and muscle. Gene set enrichment analyses indicated a downregulation of transcripts associated with extracellular matrix in muscle (family-wise error rate P < 0.01) and liver ( P = 0.04) and in transcripts associated with inflammation in muscle ( P = 0.03) in HFD + DHA compared with HFD alone. In contrast, EPA appeared to potentiate some proinflammatory effects of the HFD. In the skeletal muscle, DHA increased the expression of stress-responsive genes, whereas EPA upregulated the expression of transcripts related to cell cycle. Therefore, although both EPA and DHA supplementation during HFD partially preserve insulin signaling, they modulate distinct processes, highlighting their unique biological effects in the context of obesity.